68Ga-FAPI PET/CT to Detect Ongoing Fibroblast Activity in Post-acute COVID-19 (FAPI CLIMATE)

68Ga-FAPI PET/CT to Detect Ongoing Fibroblast Activity in Post-acute COVID-19 With Respiratory Impairment After Hospital Discharge

The goal of this observational study is to investigate the role fibroblasts play in the persistent respiratory complaints after a COVID-19 infection. Fibroblasts are involved in tissue remodeling and repair by creating scar-tissue (fibrosis) after tissue damage has occurred. The hypothesis is that this process of fibrosis is ongoing in patients with persistent complaints. To evaluate the roll of fibroblasts a new type of scan is used that is capable of imaging active fibroblasts, a 68Ga-FAPI PET/CT scan.

Study Overview

• Status: Completed
• Conditions: Pulmonary Fibrosis; Post-Acute COVID-19; Post-Acute COVID-19 Infection; Post-Acute COVID-19 Syndrome

Detailed Description

Rationale: The pathogenesis of post-acute COVID-19 with respiratory complaints remains unknown. We aim to explore the pulmonary pattern and fibrosis activity in patients with post-acute COVID-19 with respiratory complaints using 68Ga-FAPI Positron Emission Tomography-Computed Tomography (PET/CT) imaging.

Objective: To relate pulmonary fibroblast activity, measured by FAPI-PET/CT at least 3 months after hospital discharge, to interstitial lung abnormalities on high resolution CT (HRCT) at the same time point in post-acute COVID-19 patients with respiratory complaints.

Study design: This is a ZonMw funded single center prospective observational cohort study of post-acute COVID-19 patients with respiratory complaints.

Study population: We will recruit 20 adult patients, all post-ICU or post High-Flow Nasal Oxygen therapy due to there COVID-19 infection, with post-acute COVID-19 and respiratory complaints that will undergo 68Ga-FAPI PET/CT imaging to establish pulmonary fibrosis activity.

Main study parameters/endpoints: To assess the degree of Fibroblast Activation Protein expression on 68Ga-FAPI PET/CT at least 3 months after hospital discharge and to relate this to interstitial lung abnormalities on HRCT at the same time point.

• Study Type: Observational
• Enrollment (Actual): 18

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713GZ
    • University Medical Center Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults previously admitted to the ICU or ward requiring mechanical ventilation or high flow nasal oxygen due to their COVID-19 infection with now post-acute COVID-19 and respiratory complaints.

Description

Inclusion Criteria:

• Male patients >18 years and female patients >20 years discharged from hospital after PCR-confirmed COVID-19 infection.
• Previous ICU or ward admission with high flow nasal oxygen (HFNO) or mechanical ventilation.
• Persistent respiratory complaints (shortness of breath) at least 3 months after hospital discharge.

Exclusion Criteria:

• Inability or unwilling to give informed consent.
• History of claustrophobia or feeling of inability to tolerate supine position for the PET/CT scans.
• Severe or significant comorbidity, defined as COPD GOLD stage II or higher and/or known interstitial lung disease.
• Women who are pregnant or breastfeeding.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary SUV values	Based on the FAPI PET/CT scan 3-dimensinal volumes of intrest (VOI) are drawn of high FAPI uptake areas (leasions) and non-uptake areas. Using these VOIs SUV values and metabolic active volume (MAV) can be calculated which then can be used to calculate: total lesion FAPI (TL-FAPI), whole-lung FAPI-MAV (wl FAPI-MAV), wlSUVmean and whole lung TL-FAPI (wlTL-FAPI).	At time of inclusion (T0)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlate biomarkers to pulmonary SUV values	A correlation between the pulmonary FAPI uptake, reported as SUV values (see outcome 1) will be correlated with fibrosis and inflammatory specific biomarkers using Pearson's or Spearman's test.	At time of inclusion (T0)
6 minute walking test vs pulmonary SUV values	The total walked distance in meters during 6 minutes is correlated with pulmonary FAPI uptake, reported as SUV values (see outcome 1) using Pearson's or Spearman's test.	At time of inclusion (T0)
DCLO and VC vs pulmonary SUV values	Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated with DCLO and VC using Pearon's or Spearman's test.	At time of inclusion (T0)
Daily impairments (EQ-5D questionnaire) vs pulmonary SUV values	Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated with self-reported daily impairments per category as measured by the EQ-5D questionnaire using Pearson's or Spearman's test.	At time of inclusion (T0)
Cellular phenotypes	Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated to systemic and upper respiratory tract cellular phenotypes determined by single cell RNA sequencing using Pearon's or Spearmen's test.	At time of inclusion (T0)
HRCT	Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated to HRCT findings: extent of disease (0-100%), reticular pattern (0-100%), portion of groundglass (0-100%), coarness (0-3), honey combing (Yes/No), Distribution groundglass, crazy-paving pattern (Yes/No), fibrosis (Yes/No), Bronchiectasis (Yes/No), Emfyseem (Yes/No) and Pleural effusion (Yes/No).	At time of inclusion (T0)
Follow-up HRCT	Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated to HRCT findings in case of persistent respiratory complaints 8-10 months after T0. Findings that are correlated are: extent of disease (0-100%), reticular pattern (0-100%), portion of groundglass (0-100%), coarness (0-3), honey combing (Yes/No), Distribution groundglass, crazy-paving pattern (Yes/No), fibrosis (Yes/No), Bronchiectasis (Yes/No), Emfyseem (Yes/No) and Pleural effusion (Yes/No).	10 months after T0
Follow-up daily impairments (EQ-5D questionnaire) vs pulmonary SUV values	Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated with self-reported daily impairments per category as measured by the EQ-5D questionnaire using Pearson's or Spearman's test.	10 months after T0

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development
• Investigators: Principal Investigator: Riemer Slart, Prof MD PhD, University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2022
• Primary Completion (Actual): November 21, 2023
• Study Completion (Actual): May 17, 2024

Study Registration Dates

• First Submitted: June 22, 2023
• First Submitted That Met QC Criteria: August 3, 2023
• First Posted (Actual): August 8, 2023

Study Record Updates

• Last Update Posted (Actual): May 21, 2024
• Last Update Submitted That Met QC Criteria: May 19, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: HRCT; Post-ICU; 68Ga-FAPI-04; Post high-flow Nasal Oxygen therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Fibrosis; Lung Diseases, Interstitial; Chronic Disease; Post-Infectious Disorders; COVID-19; Pulmonary Fibrosis; Post-Acute COVID-19 Syndrome
• Other Study ID Numbers: 202100802

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data underlie the results reported in this article will be shared on reasonably request after deidentification of individual participant data. Only investigators whose proposed use of data is for individual participant data meta-analysis and in line with the signed informed consent are eligible for sharing. Proposals should be directed to r.h.j.a.slart@umcg.nl. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Time Frame: Directly after publication
• IPD Sharing Access Criteria: Only investigators whose proposed use of data is for individual participant data meta-analysis and in line with the signed informed consent are eligible for sharing
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No